Prenatal exposures to PCBs and methylmercury have been linked prospectively to developmental deficits in children. The data from at least one important study are controversial, however, because the children were exposed simultaneously to high levels of both contaminants. The Inuit in Canada and Greenland are among the most heavily exposed populations to these substances, due to their bioaccumulation in fish and sea mammals, staples of the Inuit diet. On the other hand, the traditional Inuit diet is also rich in omega-3 fatty acids, which are known to promote early CNS development, and in selenium, which may protect against mercury effects. We have recently conducted a study of 215 infants in Northern Quebec and are currently completing data collection on an additional 78 infants in Greenland. Although the children have been exposed to significant levels of both contaminants, the exposures are only moderately confounded in these cohorts, and preliminary data analyses suggest that each contaminant affects distinct domains of cognitive function. [unreadable] [unreadable] The proposed study will follow up these two cohorts of Inuit children at 7.5 years of age. The aims are (1) To determine more specifically which developmental endpoints are related to which contaminants; (2) To examine neural processes that may mediate the effects on these endpoints by assessing event-related potentials and eyeblink conditioning; (3) To test the hypothesis that the deficits associated with PCBs are mediated by reductions in thyroid hormone availability; and (4) To determine the degree to which omega-3 fatty acid and selenium intake can protect against these adverse effects. This study benefits from the close ties that our Canadian and Danish collaborators have forged in these Inuit communities and provides a unique opportunity to address these issues in children whose exposures are among the heaviest on earth. [unreadable] [unreadable]